The preparation and therapeutical uses of Rotigotine were first disclosed in U.S. Pat. No. 4,564,628 and U.S. Pat. No. 4,885,308. The product currently pharmaceutically used is the S enantiomeric form or its hydrochloride salt, the known syntheses of which involve 2-N-propyl-5-methoxy tetraline S enantiomer (2) as the key intermediate

which is prepared by optical resolution of the racemate according to what described in U.S. Pat. No. 4,968,837.

A number of procedures for the transformation of amine 2 into Rotigotine are disclosed. Among them, a procedure involves heating 2 in xylene with 2-thienylacetic acid and the trimethylamine-borane complex (U.S. Pat. No. 4,564,628 and Pharmaceutisch Weekblad Sci. Ed. 1985, 7, 208-211), which affords 5,6,7,8-tetrahydro-6-S-[N-propyl-2-(2-thienyl)-N-ethyl]-amino-1-methoxynaphthalene 3.
The trimethylamine-borane complex is an expensive, flammable product; therefore, this method for linking the thienylacetic chain to the secondary nitrogen of 2 is industrially problematic, due to the known instability of boron hydrides at high temperatures.
Transformation of 3 into Rotigotine, which is reported in the patents cited above and consists in hydrolyzing the methyl ether to free the phenol group, is carried out by treatment with boron tribromide at low temperature (−30° C. to −45° C.) in inert solvents. After completion of the reaction, the boron tribromide excess should be destroyed by addition of methanol, thereby forming trimethyl borate. This treatment is expensive, technically cumbersome and gives rise to polluting by-products. When using 48% hydrobromic acid under reflux for the conversion of 3 into Rotigotine, which is an established procedure for hydrolyzing phenol ethers, Rotigotine is formed together with a considerable amount of 5,6,7,8-tetrahydro-6-S-[N-(2-thienyl)-ethyl]amino-1-methoxynaphthalene 4, namely the de-alkylation product of the amino nitrogen

The structural similarity of 4 and Rotigotine makes the separation thereof through physical methods (crystallization and/or chromatography) exceedingly problematic.
It would therefore be useful to provide a process for the preparation of Rotigotine starting from the resolved amine 2 which is industrially more advantageous.